Mesenchymal neoplasms with NTRK and other kinase gene alterations

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.     

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40 , 59–74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51 , 789–808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.     

Economic impacts of care by high-volume providers for non-curative esophagogastric cancer: a population-based analysis

Gastric Cancer - Esophagogastric cancer (EGC) is one of the deadliest and costliest malignancies to treat. Care by high-volume providers can provide better outcomes for patients with EGC. Cost...     

A pilot study of levonorgestrel concentrations and bleeding patterns in women with epilepsy using a levonorgestrel IUD and treated with antiepileptic drugs

Objectives

We explored levonorgestrel (LNG) concentrations, bleeding patterns and endometrial thickness in women with epilepsy (WWE) initiating an LNG-intrauterine device (IUD) co-administered with antiepileptic drugs (AEDs).

Long-term outcomes of en-bloc renal transplantation from paediatric donors into adult recipients

Introduction

Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients.

Nebulized Ketamine Used for Pain Management of Orthopedic Trauma

BackgroundKetamine is a noncompetitive N-methyl-D-aspartate/glutamate receptor complex antagonist that decreases pain by diminishing central sensitization and hyperalgesia. When administered via i.v. (push-dose, short infusion, or continuous infusion) or intranasal routes, ketamine has shown to be effective in patients with acute traumatic pain. However, when i.v. access is not attainable or readily available, the inhalation route of ketamine administration via breath-actuated nebulizer (BAN) provides a noninvasive and titratable method of analgesic delivery. The use of nebulized ketamine has been studied in areas of postoperative management of sore throat and acute traumatic musculoskeletal and abdominal pain. To our knowledge, this is the first case series describing the use of nebulized ketamine for analgesia and orthopedic reduction.Case SeriesWe describe 4 patients who presented to the emergency department with acute traumatic painful conditions (one patellar dislocation, one shoulder dislocation, and two forearm fractures) and received nebulized ketamine for management of their pain.Why Should an Emergency Physician Be Aware of This?Administration of nebulized ketamine via BAN can be used as analgesic control for musculoskeletal trauma, as it can be administrated to patients with difficult i.v. access, has a rapid onset of analgesic effects with minimal side effects, and remains opioid-sparing.     

Total bilirubin trend as a predictor of common bile duct stones in acute cholecystitis and symptomatic cholelithiasis

Background

We hypothesized that trends in total bilirubin in the context of cholecystitis and symptomatic cholelithiasis could be used to guide testing for the presence of common bile duct stones (CBDS).